Involvement of a rapamycin-sensitive pathway in CD40-mediated activation of murine B cells in vitro

Atsuko Sakata, Kazuhiko Kuwahara, Takafumi Ohmura, Seiji Inui, Nobuo Sakaguchi

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)


Activation of resting B cells requires an initial triggering of the B cell antigen receptor (BCR) and secondary stimuli through various cytokine receptors and B cell activation molecules including CD40. We found that activation of B cells through CD40 is selectively inhibited by an immunosuppressant drug, rapamycin. This effect of rapamycin on anti-CD40- mediated activation of B cells was observed using three different in vitro assays. Rapamycin suppressed the anti-CD40-induced proliferation of splenic B cells, suppressed differentiation to surface IgM(high)/IgD(low) B cells, and inhibited an anti-CD40-mediated prevention of apoptosis induced by BCR cross- linkage of WEHI-231 cells. We next examined several known CD40 signal transduction pathways to identify the target of rapamycin in stimulated B cells. Rapamycin did not inhibit the activation of c-Jun N-terminal kinases (JNKs) induced by anti-CD40 stimulation nor the activation of immediate nuclear transcription factors of NF-κB. Therefore, rapamycin affects a novel element of the CD40 signal transduction pathway which influences the proliferation, differentiation, and prevention of apoptosis of B cells.

Original languageEnglish
Pages (from-to)301-309
Number of pages9
JournalImmunology Letters
Issue number2-3
Publication statusPublished - 01-06-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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